STM-416 for Bladder Cancer

Recruiting at 9 trial locations

Overseen By Kayti Aviano

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: SURGE Therapeutics

Must not be taking: Investigational agents

Disqualifiers: CIS, MIBC, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called STM-416 (a hydrogel-based resiquimod) to determine its safety and effectiveness for people with bladder cancer. It targets those who have undergone standard treatment but experienced a recurrence. The trial seeks participants with high-grade, non-muscle-invasive bladder cancer, a type that hasn't spread into muscle, and who are at high risk for recurrence. Participants should not have other types of bladder cancer or severe current infections. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot participate if you are receiving any other investigational agents.

Is there any evidence suggesting that STM-416 is likely to be safe for humans?

Research has shown that treatments similar to STM-416, such as TMX-101, have been safe in early studies for bladder cancer. TMX-101 is a liquid form of the medicine imiquimod, which resembles STM-416. This similarity suggests that STM-416 might also be safe. As STM-416 is in an early testing phase (Phase 1/2), researchers are primarily focused on assessing its safety. Although data may be limited, the safety of similar treatments is encouraging. The main goal of the current study is to learn more about the safety of STM-416 for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Most treatments for bladder cancer, like surgery, chemotherapy, or immunotherapy, aim to remove or kill cancer cells directly. But STM-416 works differently, targeting specific molecular pathways involved in cancer growth. This unique mechanism of action could potentially lead to fewer side effects and more effective results, especially for patients who haven't responded well to traditional therapies. Researchers are excited because STM-416 offers a novel approach that might improve outcomes and quality of life for those battling bladder cancer.

What evidence suggests that STM-416 might be an effective treatment for bladder cancer?

Research shows that STM-416 is a promising new treatment for bladder cancer. This immunotherapy aims to prevent the return and worsening of non–muscle-invasive bladder cancer (NMIBC). STM-416 releases a substance called resiquimod directly into the bladder, helping the immune system attack cancer cells. It targets specific parts of the immune system, TLR7 and TLR8, to enhance the body's natural defenses. Early results suggest that using STM-416 during surgery might reduce the risk of cancer recurrence. Although studies in humans are ongoing, the mechanism of this treatment offers strong hope for its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Seth P. Lerner

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-risk recurrent bladder cancer who are undergoing TURBT. They must have a certain level of physical fitness (ECOG 0-2) and adequate organ/marrow function. Excluded are those with invasive or carcinoma in situ bladder cancers, on other trials, allergic to similar drugs as STM-416, women who can become pregnant (only in early phases), and anyone with serious infections or unstable health conditions.

Inclusion Criteria

You are at a high risk of the condition coming back.

My blood counts and liver/kidney functions are within safe ranges.

I have had high-grade bladder cancer, treated but now recurred, and am undergoing a specific bladder tumor surgery without chemotherapy.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I may have a urinary tract infection, but it is not severe.

I am allergic to ingredients similar to those in STM-416.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Open-label, single-treatment, dose-escalation study to evaluate the safety and tolerability of STM-416 administered intraoperatively

21 days

Intraoperative administration, followed by monitoring

Treatment Phase 2a

Randomized, single-blind, single-treatment, dose-expansion study with two arms: TURBT + STM-416 Dose 1 followed by SOC versus TURBT + STM-416 Dose 2 followed by SOC

Up to 24 months

Regular follow-ups including cystoscopy and urine cytology

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days

What Are the Treatments Tested in This Trial?

Interventions

• STM-416

Trial Overview The study tests STM-416's safety and tolerability in patients with bladder cancer. It's the first time this drug is being tried on humans (Phase 1/2a). The trial involves increasing doses to find out what amount is safe and how well it works when given during TURBT surgery for recurring non-muscle-invasive bladder cancer.

How Is the Trial Designed?

Group I: STM-416 Experimental Treatment 1 Intervention

STM-416

STM-416 is already approved in United States for the following indications:

Approved in United States as SURGERx with resiquimod for:

• Prevention of recurrence and/or progression of non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT)

Who Is Running the Clinical Trial?

SURGE Therapeutics

Lead Sponsor

Trials

3

Recruited

120+

Published Research Related to This Trial

TMX-101, a novel formulation of imiquimod for intravesical delivery, was found to be safe and well tolerated in a phase 2 trial involving 12 patients with non-muscle-invasive bladder cancer, with only mild adverse effects reported.

The treatment showed potential clinical activity, as evidenced by two patients achieving negative biopsy and cytology results at 6 weeks post-treatment, along with significant increases in urinary cytokines, indicating an immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer. Donin, NM., Chamie, K., Lenis, AT., et al.[2022]

In a phase 1 trial involving 7 patients with low-grade non-muscle-invasive bladder cancer (NMIBC), TMX-101 did not achieve a complete response in any patient, indicating that the effective biologic dose could not be established.

Despite the lack of complete responses, TMX-101 was found to be safe, with all reported adverse events being of grade 2 severity or less, and no significant changes in laboratory parameters or vital signs during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic, Pharmacodynamic, and Activity Evaluation of TMX-101 in a Multicenter Phase 1 Study in Patients With Papillary Non-Muscle-Invasive Bladder Cancer. Arends, TJ., Lammers, RJ., Falke, J., et al.[2022]

The study demonstrates that combining antisense oligonucleotides targeting heat shock protein-27 (Hsp27) with the chemotherapy drug HTI-286 significantly enhances the drug's effectiveness against high-risk bladder cancer, as shown in both cell line studies and an orthotopic murine model.

This combination therapy works by inactivating the Akt signaling pathway and down-regulating Bcl-2, leading to increased chemosensitivity, and importantly, it does so without causing toxic side effects, making it a promising new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical combination treatment with antisense oligonucleotides targeting heat shock protein-27 and HTI-286 as a novel strategy for high-grade bladder cancer. Matsui, Y., Hadaschik, BA., Fazli, L., et al.[2020]

The study established rat models of bladder cancer to evaluate the effectiveness of polyanhydride-pirarubicin (PAD-THP) implants, which showed a significantly greater antitumor effect compared to the same dose of the naked pirarubicin drug.

The PAD-THP implants demonstrated improved local drug release characteristics, suggesting they could be a promising option for postoperative treatment of bladder tumors in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term anti-cancer implants inhibiting the activity of tumor growth in animal models]. Yu, M., Du, Z., Xue, J., et al.[2014]

Endovesical chemotherapy after bladder tumor removal is crucial for reducing recurrence and progression rates in non-muscle invasive bladder cancer, especially as traditional treatments like BCG and MMC have limitations.

Recent advancements in drug options and administration techniques, including hyperthermia, show promising preliminary results, suggesting a positive outlook for urologists treating bladder cancer with new and effective alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New endovesical chemotherapy and means of administration: EMD, HIVEC, Synergo, Unithermia.] Guerrero-Ramos, F., Rodríguez-Antolín, A.[2020]

In a multicenter trial involving 193 primary and 121 recurrent cases of superficial bladder cancer, the combination of 20 mg Adriamycin and 200 mg cytosine arabinoside showed a significantly higher 12-month nonrecurrence rate (86.2%) compared to the control group (68.4%), indicating its efficacy in preventing recurrence after surgery.

For recurrent cases, no significant differences in nonrecurrence rates were observed with various oral drugs, suggesting that while intravesical treatment with ADM+CA is beneficial for primary cases, further research is needed to improve outcomes for recurrent bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic chemotherapy for primary and recurrent superficial bladder cancer: preliminary results. The Hokkaido University Bladder Cancer Collaborating Group. Togashi, M., Shinohara, N., Toyota, K., et al.[2019]

In a study of 20 patients with nonmuscle invasive bladder cancer, a single intravesical instillation of apaziquone after tumor resection was well tolerated, with 65% reporting mild adverse events, primarily dysuria and hematuria.

Pharmacokinetic analyses showed that apaziquone and its active metabolite EO5a were not detected in the bloodstream, indicating a favorable safety profile and minimal systemic exposure, which supports further investigation of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer. Hendricksen, K., Gleason, D., Young, JM., et al.[2014]

The study developed a new treatment for bladder cancer using folate-modified liposomes (R-FL) encapsulated in a hydrogel, which showed enhanced cellular uptake in bladder cancer cells and improved drug retention in the bladder.

In an orthotopic bladder cancer mouse model, the R-FL/P407 formulation demonstrated significantly greater tumor growth inhibition compared to conventional liposomes, indicating its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical delivery of rapamycin via folate-modified liposomes dispersed in thermo-reversible hydrogel. Yoon, HY., Chang, IH., Goo, YT., et al.[2022]

TMX-101, a liquid formulation of imiquimod, was found to be safe for treating nonmuscle invasive bladder cancer in a phase 1 study involving 16 patients, with no serious adverse events reported during 88 instillations.

Most adverse events were mild or moderate, primarily affecting the genitourinary tract, and there was low systemic uptake of the drug, indicating a favorable safety profile compared to previous studies of imiquimod.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer. Falke, J., Lammers, RJ., Arentsen, HC., et al.[2022]

The smart gel system developed for single instillation (SI) significantly enhances the treatment of non-muscle-invasive bladder cancer by effectively preventing re-implantation of tumor cells and ablating residual tumor lesions, using a combination of photothermal therapy and chemotherapy.

This gel system adheres selectively to tumor tissues, forming a protective layer that improves retention time and efficacy of the treatment, suggesting a promising new strategy for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A gel system for single instillation of non-muscle-invasive bladder Cancer: A "divide-and-rule" strategy. Guo, P., Shang, W., Peng, L., et al.[2022]

The TransCon Hydrogel technology enables sustained release of anti-cancer drugs directly into tumors, allowing for high local drug concentrations while minimizing systemic exposure, which could enhance efficacy and reduce side effects.

This method has been shown to effectively release drugs like resiquimod and axitinib over several weeks, and a hydrogel prodrug of resiquimod is currently being tested in clinical trials for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Degradable Hydrogel for Sustained Localized Delivery of Anti-Tumor Drugs. Lessmann, T., Jones, SA., Voigt, T., et al.[2023]

In a study of 127 non-muscle invasive bladder cancer patients, the combination of pirarubicin and hyaluronic acid significantly improved relief from pelvic pain and urinary symptoms compared to pirarubicin alone, with notable improvements observed within the first month (P = 0.04).

While the combination treatment did not show a significant difference in preventing cancer recurrence, it was deemed safe, with no adverse events related to hyaluronic acid, indicating it could be a beneficial addition to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pirarubicin combined with hyaluronic acid for non-muscle invasive bladder cancer after transurethral resection: a prospective, randomized study. Huang, W., Wang, F., Wu, C., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05710848

A Study of STM-416 Administered to Patients Undergoing ... This is a 2-part, multicenter, first-in-human (FIH), Phase 1/2a study in patients with a history of pathologically confirmed high-grade Ta or T1 NMIBC ...

2. bcan.org bcan.org/clinicaltrials/stm-416-administered-to-patients-undergoing-turbt-for-recurrent-bladder-cancer/

STM-416 Administered to Patients Undergoing TURBT for ... This study is investigating a new kind of immunotherapy called STM-416, which can be applied to your bladder during the TURBT procedure to deliver the therapy ...

3. withpower.com withpower.com/trial/phase-2-urinary-bladder-neoplasms-2-2023-15cad

STM-416 for Bladder Cancer This trial tests STM-416, a new treatment, in bladder cancer patients whose disease has returned after standard treatments.

4. urologytimes.com urologytimes.com/view/fda-accepts-investigational-new-drug-application-for-nmibc-immunotherapy

FDA accepts investigational new drug application for ... The treatment works to prevent recurrence and/or progression of non–muscle-invasive bladder cancer (NMIBC) following transurethral resection of ...

5. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/hydrogel-based-resiquimod-stm-416

Definition of hydrogel-based resiquimod STM-416 ... bladder tumor, the hydrogel-based resiquimod STM-416 locally releases resiquimod for an extended period and binds to TLR7 and 8, which are found mainly on ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-07329

A Study of STM-416 Administered to Patients Undergoing ... This is a first-in-human (FIH), Phase 1/2a, multi center, open-label, single treatment, dose escalation and expansion study designed to determine the safety ...